The Transgenic and Embryonic Stem Cell Facility is a shared facility designed to generate transgenic and knockout mice for researchers at the University of Chicago. Most of these experiments are being conducted by members of the University of Chicago Cancer Center, and many of these experiments have direct implications not only for our understanding of cancer, but also for generating animal model systems that will be important for developing new and improved diagnostic and therapeutic tools for cancer. Five services are currently provided by the Facility: (1) preparation of transgenic mice, through the F1 generation; (2) transfer of embryonic stem cells to mouse blastocysts, and subsequent generation of chimeric, heterozygous and homozygous mice targeted for a particular null mutation, (3) embryo freezing; (4) timed mouse pregnancies, and (5) clean mouse strain rederivation from either frozen embryos or embryos obtained from non-pathogen free mice; . Projects carried out by the facility have been funded by a peer-reviewed federal or private grant, and the experimental protocol receives prior approval from the University IACUC. Projects include: (1) altering signal transduction pathways and cell-cell adhesion in stratified squamous epithelia, and examining the relation of these alterations to hyperproliferative disorders and skin cancers; (2) altering the expression of cell survival and death factors in mice and examining the molecular consequences; (3) perturbing growth control and inflammatory responses in cells of the immune system; (4) examining the roles of chromosomal breakpoint genes on tumorigenesis; (5) examining the functions of transcription factors on stem cell maintenance, cell-type specific gene expression, development and differentiation, and assessing the biological consequences and relevance to cancer when they are misregulated; and (6) exploring mechanisms of somatic hypermutation of genes in B-cell development. These studies have been central to the investigative goals of cancer researchers on campus; the contributions are of fundamental importance to our understanding of cancer.